RESUMEN
Photooxidation of aryl(hetaryl)pyrazolines in the presence of benzoquinone has been studied in organic solvents. This reaction occurs at high rate to provide the corresponding pyrazole in a good yield. The effects of the solvent, pyrazoline structure and oxygen provide definite information on the reaction pathway. It appears that radical species are intermediates in the photooxidation of aryl(hetaryl)pyrazolines in the presence of benzoquinone. A comparison of the new results with the photooxidation of aryl(hetaryl)pyrazolines in the presence of perchloroalkanes is also discussed.
RESUMEN
New (1,5-diaryl-3-pyrazolinyl)coumarins have been synthesized. The compounds do not undergo keto-enol tautomeric transformations with changes in the solvent. (1,5-Diaryl-3-pyrazolinyl)coumarins provide dehydrogenation reaction under irradiation in the presence of perchloroalkanes and manifest themselves as effective photogenerators of acidity. Several aspects of photodehydrogenation mechanism have been studied. Oxygen is shown not be involved in the reaction. Polar solvents increase rate of the reaction. The measured rate constants of the photodehydrogenation reactions vary in a significant range according to the structure of pyrazoline. The data correlate with ionization potentials of pyrazolines available from DFT quantum chemical calculations. These results are discussed in terms of proposed scheme of mechanism of pyrazolines photodehydrogenation assuming formation of ion-radical and ion intermediates.
RESUMEN
A series of novel non-symmetrical coumarin-fused BODIPY dyes were synthesised. Their absorption and emission properties are strongly influenced by substitution in the coumarin moiety. Diethylamino-substituted dyes showed near-IR emission with large Stokes shifts (up to 144 nm) and good fluorescence quantum yields.
RESUMEN
We developed the synthesis of a series of furan-fused tetracyclic analogues of the antitumor agent ametantrone. The reactions included nucleophilic substitution of propoxy groups in 4,11-dipropoxyanthra[2,3-b]furan-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b]furan-5,10-dione in good yields. Studies of anti-proliferative activity on a panel of mammalian tumor cell lines demonstrated that anthra[2,3-b]furan-5,10-diones were the most potent derivatives among heteroarene-fused ametantrone analogues with one heteroatom. We identified several compounds that evoked a growth inhibitory effect at submicromolar concentrations. The anthra[2,3-b]furan-5,10-dione 9 with distal methylamino groups was markedly potent against drug-resistant cell lines with P-glycoprotein overexpression or p53 gene deletion. Furthermore, this derivative attenuated in vitro topoisomerase I-mediated DNA uncoiling at low micromolar concentrations. These results demonstrate that anthrafurandiones are a new class of heterocyclic anthraquinone derivatives with the properties potentially valuable for anticancer therapy.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Furanos/síntesis química , Furanos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , ADN/química , ADN/metabolismo , ADN-Topoisomerasas de Tipo I/metabolismo , Resistencia a Antineoplásicos , Furanos/química , Humanos , Concentración 50 Inhibidora , Conformación de Ácido Nucleico/efectos de los fármacos , Pirroles/química , Tiofenos/químicaRESUMEN
HIV-1 integrase (IN) has emerged as an important therapeutic target for anti-HIV drug development. Its uniqueness to the virus and its critical role in the viral life cycle makes IN suitable for selective inhibition. The recent approval of Raltegravir (MK-0518) has created a surge in interest and great optimism in the field. In our ongoing IN drug design research, we herein report the discovery of substituted analogs of 3-acetyl-4-hydroxy-2-pyranones and their difluoridoborate complexes as novel IN inhibitors. In many of these compounds, complexation with boron difluoride increased the potency and selectivity of IN inhibition. Compound 9 was most active with an IC(50) value of 9 microM and 3 microM for 3'-processing and strand transfer inhibition, respectively.
Asunto(s)
Compuestos de Boro/farmacología , Fluoruros/farmacología , Inhibidores de Integrasa VIH/farmacología , VIH-1/efectos de los fármacos , Pironas/farmacología , Algoritmos , Secuencia de Bases , Compuestos de Boro/síntesis química , Línea Celular , Neoplasias del Colon/enzimología , Neoplasias del Colon/patología , Fluoruros/síntesis química , Inhibidores de Integrasa VIH/síntesis química , VIH-1/enzimología , Humanos , Concentración 50 Inhibidora , Pironas/síntesis química , Pirrolidinonas/farmacología , Raltegravir Potásico , Relación Estructura-ActividadRESUMEN
Novel photochromic 5-(3'-coumarinyl)-4-(3''-thienyl)thiazoles have been synthesized. These compounds display intensive fluorescence emission in the open form A, which is modulated by light. Fluorescence intensity decreases significantly upon irradiation of A with UV-light (lambda<400 nm) due to formation of the cyclic form B. Irradiation of B with visible light (lambda>470 nm) promotes its opening and the recovering of fluorescence. Novel dihetarylethenes undergo photochromic modulation of fluorescence both in solution and in polymeric matrices.
RESUMEN
Many furocoumarins and their analogs possess a prominent photobiological activity. Some of them are successfully used as drugs in phototherapy of skin diseases. Fries rearrangement of acyloxyheteroarenes, condensation of acylhydroxyheteroarenes with alpha-carbonyl compounds under base catalysis and transformations of dihydrofurocoumarinones are new trends in synthesis of furocoumarins and their analogs.